Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574718 | SCV000676359 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-01-11 | criteria provided, single submitter | clinical testing | The c.7692dupG variant, located in coding exon 15 of the APC gene, results from a duplication of G at nucleotide position 7692, causing a translational frameshift with a predicted alternate stop codon (p.R2565Efs*18). Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of APC, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 262 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV003537213 | SCV000932880 | pathogenic | Familial adenomatous polyposis 1 | 2020-08-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 487047). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Arg2565Glufs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 279 amino acids of the APC protein. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. This variant disrupts the C-terminus of the APC protein. Other variant(s) that disrupt this region (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV002530356 | SCV004045775 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |